Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_001754.5(RUNX1):c.492C>T (p.Val164=)

CA10014503

239049 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 878af985-af5d-4586-a9f0-6e51f11a15b5

HGVS expressions

NM_001754.5:c.492C>T

NM_001754.5(RUNX1):c.492C>T (p.Val164=)

NC_000021.9:g.34880573G>A

CM000683.2:g.34880573G>A

NC_000021.8:g.36252870G>A

CM000683.1:g.36252870G>A

NC_000021.7:g.35174740G>A

NG_011402.2:g.1109139C>T

ENST00000675419.1:c.492C>T

ENST00000300305.7:c.492C>T

ENST00000344691.8:c.411C>T

ENST00000358356.9:c.411C>T

ENST00000399237.6:c.456C>T

ENST00000399240.5:c.411C>T

ENST00000437180.5:c.492C>T

ENST00000482318.5:c.*82C>T

NM_001001890.2:c.411C>T

NM_001122607.1:c.411C>T

NM_001754.4:c.492C>T

NM_001001890.3:c.411C>T

NM_001122607.2:c.411C>T

Likely Benign

BP4 BP7

PS4 PS2 PS1 PS3 BA1 PP1 PP4 PP3 PP2 PM5 PM1 PM3 PM4 PM6 PM2 PVS1 BS2 BS4 BS3 BS1 BP2 BP3 BP1 BP5

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Myeloid Malignancy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.492C>T (p.Val164=) is a synonymous variant. No REVEL score because a synonymous variant and SpliceAI is ≤0.20( 0.01 Donor Loss -16bp and 0.11 Donor Gain 7bp) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP 1.91014 ≤ 2.0) meeting BP7. In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and BP7.

BP4

No REVEL score because a synonymous variant and SpliceAI is ≤0.20( 0.01 Donor Loss -16bp and 0.11 Donor Gain 7bp)

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP 1.91014 ≤ 2.0)

PS4

Evidence does not support this assertion

PS2

No case studies found

PS1

Amino acid has not been previously been established as pathogenic

PS3

Evidence not found.

BA1

MAF 0.001786 (0.17%, 18/10080, 18 alleles) in Ashkenazi Jewish subpopulation in gnomAD.

PP1

Case studies not found.

PP4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP3

No REVEL score because a synonymous variant and SpliceAI Donor Loss -16bp (0.01) and Donor Gain 7bp (0.11) is not ≥0.38

PP2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM5

Not a missense variant

PM1

Not a missense variant

PM3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM4

Not an in-frame deletion/insertion

PM6

No case studies found

PM2

MAF 0.001786 (0.17%, 18/10080, 18 alleles) in Ashkenazi Jewish subpopulation in gnomAD.

PVS1

Not a null variant

BS2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS4

Case studies not found.

BS3

Evidence not found.

BS1

MAF 0.001786 (0.17%, 18/10080, 18 alleles) in Ashkenazi Jewish subpopulation in gnomAD.

BP2

No homozygotes observed in gnomAD population (v2 and v3)

BP3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2022-07-05

Published on: 2022-07-05

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